Cytoreductive radiotherapy combined with abiraterone in metastatic castration-resistance prostate cancer: a single center experience.

BACKGROUND: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone. METHODS: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group). RESULTS: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR 0.17; 95% CI 0.05-0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI 1.37-5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤ 65 years (HR 0.09; 95% CI 0.01-0.65; P = 0.018), PSA ≤ 20 ng/mL (HR 0.29; 95% CI 0.09-0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI 0.06-0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI 0.03-0.57; P = 0.007) had improved OS with AbiRT. CONCLUSIONS: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤ 65 years old, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC and intermediate prognosis.

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The role of local radiotherapy in metastatic castration-resistant prostate cancer (mCRPC) remains undefined. This study aimed to identify the value of local radiotherapy and potential candidates for mCRPC. METHODS: A total of 215 patients with mCRPC treated with or without cytoreductive radiotherapy (CRT) between June 2011 and February 2019 were analyzed. Overall survival (OS) was calculated from the onset of mCRPC. The receiver-operating characteristic (ROC) curve was used to find the cutoff point for time to castration resistance (TCR). RESULTS: One-hundred and fifty-five (72.1%) patients received abiraterone after mCRPC, and 54 (25.1%) patients received CRT. The median TCR was 14.9 months. After a median follow-up of 31.7 months, the median OS was 33.3 months. The Eastern Cooperative Oncology Group (ECOG) performance scores 0-1, oligometastases, abiraterone after mCRPC, CRT, and TCR ≥9 months were independent prognostic factors for better OS. Stratified analyses showed improved survival when CRT was applied to patients treated with abiraterone (HR 0.44; 95% CI 0.23-0.83; P = 0.012) and TCR ≥9 months (HR 0.39; 95% CI 0.21-0.74; P = 0.004). The percentage of PSA response after radiotherapy was higher in patients with TCR ≥9 months compared to those with TCR <9 months. No grade 3 or worse adverse events after radiotherapy were reported. CONCLUSIONS: ECOG performance score, oligometastases, abiraterone application, TCR and CRT were independent prognostic factors for OS in patients with mCRPC. Patients with a short duration of response to primary androgen deprivation therapy were less likely to benefit from CRT.

Application of dose-volume histogram prediction in biologically related models for nasopharyngeal carcinomas treatment planning.

PURPOSE: In this study, we employed a gated recurrent unit (GRU)-based recurrent neural network (RNN) using dosimetric information induced by individual beam to predict the dose-volume histogram (DVH) and investigated the feasibility and usefulness of this method in biologically related models for nasopharyngeal carcinomas (NPC) treatment planning. METHODS AND MATERIALS: One hundred patients with NPC undergoing volumetric modulated arc therapy (VMAT) between 2018 and 2019 were randomly selected for this study. All the VMAT plans were created using the Monaco treatment planning system (Elekta, Sweden) and clinically approved: > 98% of PGTVnx received the prescribed doses of 70 Gy, > 98% of PGTVnd received the prescribed doses of 66 Gy and > 98% of PCTV received 60 Gy. Of these, the data from 80 patients were used to train the GRU-RNN, and the data from the other 20 patients were used for testing. For each NPC patient, the DVHs of different organs at risk were predicted by a trained GRU-based RNN using the information given by individual conformal beams. Based on the predicted DVHs, the equivalent uniform doses (EUD) were calculated and applied as dose constraints during treatment planning optimization. The regenerated VMAT experimental plans (EPs) were evaluated by comparing them with the clinical plans (CPs). RESULTS: For the 20 test patients, the regenerated EPs guided by the GRU-RNN predictive model achieved good consistency relative to the CPs. The EPs showed better consistency in PTV dose distribution and better dose sparing for many organs at risk, and significant differences were found in the maximum/mean doses to the brainstem, brainstem PRV, spinal cord, lenses, temporal lobes, parotid glands and larynx with P-values < 0.05. On average, compared with the CPs, the maximum/mean doses to these OARs were altered by - 3.44 Gy, - 1.94 Gy, - 1.88 Gy, 0.44 Gy, 1.98 Gy, - 1.82 Gy and 2.27 Gy, respectively. In addition, significant differences were also found in brainstem and spinal cord for the dose received by 1 cc volume with 4.11 and 1.67 Gy dose reduction in EPs on average. CONCLUSION: The GRU-RNN-based DVH prediction method was capable of accurate DVH prediction. The regenerated plans guided by the predicted EUDs were not inferior to the manual plans, had better consistency in PTVs and better dose sparing in critical OARs, indicating the usefulness and effectiveness of biologically related model in knowledge-based planning.

Survival Outcomes After Adding Stereotactic Body Radiotherapy to Metastatic Renal Cell Carcinoma Patients Treated With Tyrosine Kinase Inhibitors.

OBJECTIVE: Long-lasting control is rarely achieved with tyrosine kinase inhibitors (TKI) alone in metastatic renal cell carcinoma (mRCC). Our study aimed to investigate the survival outcomes of adding stereotactic body radiotherapy (SBRT) to TKI in mRCC. MATERIALS AND METHODS: From September 2015 to September 2018, 56 patients treated with TKI received SBRT for 103 unresectable lesions. A total of 24 and 32 patients were irradiated before and after TKI failure, respectively. Overall survival (OS) was calculated from metastases. Progression-free survival (PFS) was calculated from SBRT. RESULTS: Overall, 10, 32, and 12 patients had International Metastatic Renal Cell Carcinoma Database Consortium favorable, intermediate, and poor risk. Median follow-up was 21.7 months (range, 5.1 to 110.6 mo). Median OS was 61.2 months. The median PFS was 11.5 months, while the 2-year LC rate was 94%. Sixteen (34%) lesions achieved complete response (CR) in patients irradiated before TKI failure, whereas only 4 (7%) lesions yielded CR in those irradiated after TKI failure (P=0.001). The median PFS in CR group was significantly longer than that of non-CR group (18.9 vs. 7.1 mo; P=0.003). The 5-year OS in CR group was 86%, compared with 48% in non-CR group (P=0.010). Four (7%) patients experienced Grade 3 toxicity. CONCLUSIONS: Adding SBRT to TKI is safe and seems to improve survival in mRCC. Patients irradiated before TKI failure have higher CR rate, and the favorable local response might turn into survival benefit.

Clinical evaluation for the difference of absorbed doses calculated to medium and calculated to water by Monte Carlo method.

BACKGROUND: To evaluate the difference of absorbed doses calculated to medium and to water by a Monte Carlo (MC) algorithm based treatment planning system (TPS), and to assess the potential clinical impact to dose prescription. METHODS: Thirty patients, 10 nasopharyngeal cancer (NPC), 10 lung cancer and 10 bone metastases cases, were selected for this study. For each case, the treatment plan was generated using a commercial MC based TPS and dose was calculated to medium (Dm). The plan was recalculated for dose to water (Dw) using the same Monitor Units (MU) and control points. The differences between Dm and Dw were qualitatively evaluated by dose-volume parameters and by the plan subtraction method. All plans were measured using the MapCheck2, and gamma passing rates were calculated. RESULTS: For NPC and Lung cases, the mean differences between Dw and Dm for the targets were less than 2% and the maximum difference was 3.9%. The maximum difference of D2% for the organs at risk (OARs) was 6.7%. The maximum differences between Dw and Dm were as high as 10% in certain high density regions. For bone metastases cases, the mean differences between Dw and Dm for the targets were more than 2.2% and the maximum difference was 7.1%. The differences between Dw and Dm for the OARs were basically negligible. At 3%&3 mm criterion, the gamma passing rate of Dw plan and Dm plan were close (> 94%). CONCLUSION: The differences between Dw and Dm has little clinical impact for most clinical cases. In bony structures the differences may become clinically significant if the target/OAR is receiving doses close to its tolerance limit which can potentially influence the selection or rejection of a particular plan.

[Correction of enhanced dynamic wedge factor and analysis of monitor unit calculation].

OBJECTIVE: To study the correction of algorithm for Varian enhanced dynamic wedge(EDW) factors and compare the dose/monitor unit (MU) deviation measured at the central axis of EDW field with that obtained by manual calculation or using the treatment planning system. METHODS: EDW factors and dose were measured with Thimble ion chamber at 10 cm depth under the water for 6 MV and 10 MV photon on Varian linear accelerator. The corresponding calculations were done with the radiation treatment planning system. An analytic formula, namely the MU Fraction model, was used to calculate the EDW factor, which was corrected with a constant factor. The MU of conventional 2-D planning derived from manual calculating, treatment planning system, and actual measurements were compared. RESULTS: With the measured results as the standard, the corrected manual calculation deviation of EDW factors was significantly reduced. For photon 6 MV, the maximum deviation reduced from 4.2% to 1.3% for 60° symmetry fields was, and from -4.7% to -1.8% for asymmetric fields. For photon 10 MV, the maximum deviation for all EDW fields was reduced from -3.0% to 1.1%. Comparison of the manual calculations with the measured results showed a MU deviation for symmetric fields within 2%, and more than 5% for some asymmetric fields. The deviation between the calculations of the treatment planning and the measured results was less than 1.5%. CONCLUSION: Constant factor correction can effectively reduce the deviation of manual calculation. For MU calculation of EDW field in conventional 2-D dimensional treatment planning, the corrected results of symmetric fields meet clinical requirements. While the minimum distance between the field edge and the central axis was less than 4 cm in asymmetric fields, the corresponding special method, measurement or the treatment planning system should be used to calculate the dose/MU.

A comparison of VMAT dosimetric verifications between fixed and rotating gantry positions.

This study comparatively analysed dose distributions between the fixed and rotating gantry positions of volumetric-modulated arc therapy (VMAT) plans measured using different dosimetric techniques with the intent to provide pre-treatment quality assurance (QA). A total of 12 VMAT plans for the treatment of anatomical sites of various complexities were chosen. An ion chamber was used to measure the absolute central point doses, while EPID, Seven29, Matrixx and Delta4 were used to measure the dose distributions. With the exception of Delta4, all detectors were used in one of two different settings: the gantry was either fixed at 0°, or the gantry was rotating. The results were analysed using the γ-evaluation method. Regarding absolute central point doses, the ion chamber results were within 3% of the treatment planning system (TPS) calculated results. For the dose distributions measured by detectors and calculated by TPS, the γ pass rates, with 3% maximum dose and 3 mm γ criteria, were above 96% when the gantry was fixed at 0°. When the gantry was rotating, the pass rates decreased slightly but were still above 90%. The results obtained from the comparison between the measured and calculated doses demonstrated the reliability of four detectors associated with VMAT. However, the treatment delivery and detector response may impact the results when the gantry is rotating.